Currently, the research and development of pharmaceutical industry, particularly antibiotic, is facing difficulties: 1. There are more and more drug-resistant pathogenic bacteria. Current antibiotics do not pose a threat to drug-resistant pathogenic bacteria. Mortality rate caused by these drug-resistant pathogenic bacteria is increasing. 2. The speed of novel medicine developing is far behind the occurring pace of drug-resistant pathogenic bacteria. It needs long time and costs much to screen antibiotics with traditional methods as well as obtain the achievement from the research and development. 3. The novel antibiotics developed by gene engineering or biotechnology are still easy to result in drug-resistance of pathogenic bacteria.
It was shown by statistics data of World Health Organization (WHO) that, in millions of people infected with drug-resistant Staphylococcus aureus every year, around 30% of said people die finally—which is higher than the mortality rate of AIDS. In order to cure infection of drug-resistant Staphylococcus aureus, the cost of whole world exceeds 20 billion USD every year. After drug-resistant Staphylococcus aureus occurred, vancomycin became the main role to cure Staphylococcus aureus infection. However, there has been vancomycin-resistant Staphylococcus aureus occurred in hospital since 2002. Although the spreading area of vancomycin-resistant Staphylococcus aureus is small at present, there is little medicine that can inhibit them effectively, so the mortality rate caused by infection of vancomycin-resistant Staphylococcus aureus is very high. In the latest 10 years, another drug-resistant bacteria—multi-drug-resistant Gram-negative bacteria occurred, and they have stronger drug-resistance. Almost none of antibiotics used in current clinical medicine can threaten said drug-resistant bacteria.
Currently most of antibiotics are produced by bacteria and fungi, or derived from natural antibiotics by chemical modification. The traditional screening method for antibiotics comprises isolating microorganisms from soil samples, extracting secretions from medium for growing said microorganisms, detecting substance with antibacterial or sterilizing effects in said secretions and separating individual medicine ingredients with potential medicinal value. The method was very effective in golden age of developing antibiotics (1940-1950). But it comes to the end now, as said screening method depends on secretions of bacteria and fungi in nature, namely the novel antibiotics are obtained by screening and modifying secretions of discovered microorganisms. Said traditional method for developing antibiotics requires long time unavoidably, and has uncertain outcome. Thus, in the past 50 years, pharmaceutical companies never stopped screening antibiotics, but novel antibiotics screened are less and less. It is demonstrated by statistics data of Infectious Diseases Society of America (IDSA) that, in recent new medicine applications of FDA in US, there are only 16 novel antibiotics applications, and there is no one patent application about antibiotic against highly-drug-resistant Gram-negative bacteria. The famous popular science magazine “Scientific American” had warned continuously from 2009 to 2012 that, super bacteria are threatening human life safety. CDC in US forecast that the current used antibiotics would become invalid totally 10-20 years later. The New York Times reports that, due to abusing antibiotics in agriculture, human would go back to the times without any available antibiotics 5 years later, and NDM-1 super bacterium mutant genes has led to panic in the world. The problem of antibiotics and drug-resistant bacteria in stockbreeding is also a serious problem, and has influenced agricultural product safety. The recent 40 years is a vacuum period of antibiotics development. In a word, the speed of developing and researching novel medicine is far behind the pace of drug-resistant bacteria mutation.
At present, there are two methods for developing novel antibiotics: (1) modifying current antibiotics or synthesizing new type of antibiotics, (2) conducting gene modification on bacteria synthesizing antibiotics. However, both of said two methods have not overstepped such a keynote that: antibacterial mechanism of said antibiotics is not novel to bacteria. Therefore, without exception, the bacteria will generate drug-resistance to said “novel” antibiotics soon.
In order to resist pathogenic microorganisms with strong variability, strong viability, strong pathogenicity and various species, the problems urgent to be solved currently are as follows:
1. providing antibiotics with stronger antibacterial or sterilizing effects to pathogenic bacteria, especially to drug-resistant pathogenic bacteria;
2. providing methods for preparing said antibiotics in clause 1, preferably methods which can response to variability of pathogenic bacteria, i.e., developing and researching methods of antibiotics with short development cycle, which can sensitively resist new or variant pathogenic microorganisms;
3. said antibiotics developed by said method will not lead to drug-resistance of pathogenic microorganisms in a short time.
However, the above-mentioned problems are just “conundrums” which have not been solved by current several generations of antibiotics and traditional antibiotics developing methods.